INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.
- MeSH
- Bariatric Surgery * MeSH
- Time Factors MeSH
- Equipment Design MeSH
- Adult MeSH
- Elasticity Imaging Techniques MeSH
- Weight Loss MeSH
- Liver Cirrhosis * etiology diagnostic imaging diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Non-alcoholic Fatty Liver Disease * diagnostic imaging diagnosis etiology MeSH
- Obesity * complications surgery diagnosis MeSH
- Pilot Projects MeSH
- Prospective Studies MeSH
- Treatment Outcome MeSH
- Gastric Balloon * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.
- MeSH
- Action Potentials MeSH
- Bundle-Branch Block * physiopathology therapy diagnosis MeSH
- Time Factors MeSH
- Cardiomyopathy, Dilated physiopathology therapy diagnosis MeSH
- Electrocardiography * MeSH
- Ventricular Function, Left * MeSH
- Hemodynamics * MeSH
- Middle Aged MeSH
- Humans MeSH
- Predictive Value of Tests * MeSH
- Cardiac Resynchronization Therapy Devices MeSH
- Aged MeSH
- Heart Rate MeSH
- Cardiac Resynchronization Therapy * MeSH
- Heart Failure physiopathology therapy diagnosis MeSH
- Stroke Volume MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.
- MeSH
- Mediation Analysis * MeSH
- Adult MeSH
- Smoking * epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Lung Neoplasms * epidemiology MeSH
- Odds Ratio MeSH
- Risk Factors MeSH
- Aged MeSH
- Social Class * MeSH
- Case-Control Studies MeSH
- Bias * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.
- MeSH
- alpha-Galactosidase * administration & dosage therapeutic use MeSH
- Adult MeSH
- Enzyme Replacement Therapy * methods MeSH
- Fabry Disease * drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Polyethylene Glycols administration & dosage MeSH
- Recombinant Proteins * administration & dosage therapeutic use MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Sphingolipids blood MeSH
- Trihexosylceramides blood MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
The largest obstacle in the promotion of biopesticides is the existence of counterfeit products available in the market. Identification and quantification of antagonistic organisms in biopesticide products are the key to the reduction of spurious microbial pesticides. In this study, we have developed a simple, sensitive, isothermal-based colourimetric assay for specific detection of Bacillus subtilis from the biopesticide formulations and soil samples. A region specific to B. subtilis which codes for shikimate dehydrogenase was identified through in silico analysis. We employed conventional PCR, loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and qPCR for specific detection of B. subtilis in soil samples and biopesticide formulations. Specificity tests showed that the PCR primers amplified an amplicon of 521 bp in four strains of B. subtilis only, and no amplification was found in negative control samples. Similarly, the LAMP assay showed sky blue colour in all four strains of B. subtilis and violet colour in negative control samples. Whereas in the RPA assay, upon the addition of SYBR Green dye, a bright green colour was seen in B. subtilis strains, while a brick-red colour was observed in negative control samples by visualizing under a UV transilluminator. The qPCR assay showed specific amplifications with a Ct value of 12 for B. subtilis strains and no amplification in negative control samples. In the sensitivity test, PCR could amplify DNA of B. subtilis up to 500 pg/μL. DNA concentration as low as 10 pg/μL was enough to show the colour change in the LAMP as well as the RPA assays, whereas the qPCR assay showed sensitivity till 100 pg/μL. All four diagnostic assays developed in the study have been validated in soil samples and B. subtilis-based biopesticides. Compared to conventional PCR, the qPCR assay has the advantage of quantification and visualizing the result in real-time, whereas LAMP and RPA assays have the benefits of being colourimetric and less time-consuming. The other advantages are that the results can be visualized with the naked eye, and these assays do not require a costly thermal cycler and gel documentation system. Hence, LAMP and RPA assays are highly suitable for developing point-of-need diagnostic kits and, in turn, help regulators assess the quality of biopesticides in the market.
- MeSH
- Alcohol Oxidoreductases * genetics MeSH
- Bacillus subtilis * genetics isolation & purification enzymology MeSH
- Bacterial Proteins genetics MeSH
- Molecular Diagnostic Techniques * methods MeSH
- Colorimetry * methods MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Soil Microbiology MeSH
- Sensitivity and Specificity MeSH
- Nucleic Acid Amplification Techniques * methods MeSH
- Publication type
- Journal Article MeSH
Cíl: Používání filtroventrilačních systémů v městských autobusech ve vyspělých zemích zvyšuje komfort a kvalitu vnitřního ovzduší v prostředcích pozemní dopravy. Mikrobiální kontaminace byla studována na výstupních a vstupních plochách 5 vzduchových filtrů vyjmutých z klimatizačního systému městských autobusů při pravidelné údržbě. Materiál a metodika: K získání vzorků z výstupní i vstupní strany filtrů byla použita technika suchého stěru. Kultivace byla provedena na různých selektivních nebo selektivně-diagnostických půdách pro kultivaci životaschopných bakterií. K identifikaci bakteriálních druhů bylo použito barvení podle Grama a imerzní mikroskopie. Vybrané kolonie byly rovněž podrobeny proteomické studii. Po identifikaci byly bakterie kvantifikovány. Výsledky: Na vstupním i výstupním povrchu filtrů převažovaly bakterie rodu Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus. Identifikovány byli také bakterie rodů Staphylococcus, Brevibacillus, Peribacillus a Paenibacillus. Kvantifikace ukázala nízkou kontaminaci výstupních povrchů filtrů 1 a 2. Kontaminace vstupní a výstupní strany filtrů 3, 4 a 5 a odhalila téměř stejnou kontaminaci vstupních a výstupních ploch. Závěry: Podle nalezených výsledků doporučujeme buď častější výměnu filtrů, nebo volbu filtrů s nižší porozitou.
The use of HVAC in urban buses in developed countries increases the comfort and indoor air quality in the means of ground transportation. The microbial contamination was studied on outlet and inlet surfaces of 5 air filters removed from the urban buses HVAC during regular maintenance. To acquire samples from both the outlet and the inlet sides of the filters, dry swabbing technique was used. Cultivation was performed on different selective or selective-diagnostic agars, to cultivate viable bacteria. To identify the bacterial species, Gram stain and immerse microscopy was used. Selected colonies underwent the proteomic study (MALDI-TOF) as well. After identification, bacteria were quantified. The bacteria of the genus Bacillus – Bacillus cereus, Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus flexus prevailed on both inlet and outlet surfaces of the filters. The members of genera Staphylococcus, Brevibacillus, Peribacillus or Paenibacillus were also identified. The quantification of colony forming units showed low contamination of the outlet surfaces of filters 1 and 2. The contamination of inlet and outlet sides of filters 3, 4, and 5 was comparable, revealed nearly the same contamination of inlet and outlet surfaces. In the case of filters 3, 4 and 5 we recommend more frequent filter changing or more efficient filter choice.
Úvod: Analýza tělesného složení pomocí ct vyšetření se v současnosti ukazuje jako významný prognostický nástroj u pacientů s indikací k transkatétrové implantaci aortální chlopně (tAVi). Její rutinní využití v klinické praxi je však limitováno složitostí dostupného softwaru a vysokými technickými nároky. naším cílem bylo vyvinout a validovat webovou aplikaci, která by zjednodušila používání existujícího softwaru AutoMAticA při hodnocení tělesného složení v rámci předintervenčního vyšetření před tAVi. Metody: Vyvinuli jsme webové rozhraní integrující již validovaný software AutoMAticA, který využívá umělou inteligenci pro automatickou segmentaci tkání. Systém analyzuje předintervenční ct snímky a auto- maticky vypočítává index kosterního svalstva, objem viscerálního a podkožního tuku. Aplikace zpracovává soubory DicoM a generuje přehledné reporty včetně segmentovaných snímků a kvantitativních parametrů. Výsledky: testování systému prokázalo průměrnou dobu analýzy 21 sekund od nahrání snímků po zobrazení výsledků. uživatelské hodnocení pěti klinickými lékaři potvrdilo jednoduchost použití a klinickou využitel- nost. Analýza ilustrativních případů odhalila významné rozdíly mezi hodnocením pomocí BMi a ct analýzou tělesného složení, například u případů sarkopenické obezity nebo zachované svalové hmoty, které by při použití samotného BMi zůstaly neodhaleny. Závěr: Vyvinuté uživatelské rozhraní představuje praktické řešení pro hodnocení tělesného složení u pacientů před tAVi. Systém efektivně překlenuje mezeru mezi pokročilými analytickými možnostmi validovaného softwaru AutoMAticA a klinickou praxí díky intuitivnímu uživatelskému rozhraní. toto řešení by mělo v budoucnu umožnit přesnější stratifikaci rizika a individualizovanější přístup k pacientům s indikací k TAVI.
Background: CT-derived body composition analysis has emerged as a powerful prognostic tool for TAVI patient outcomes. However, widespread clinical implementation remains limited by complex software requirements and technical expertise barriers. This study aims to develop and validate an accessible web-based interface that streamlines the implementation of existing AutoMATiCA's validated CT-based body composition assessment in the pre-TAVI evaluation workflow. Methods: We developed a web-based interface integrating the validated AutoMATiCA's AI-driven segmentation software for automated body composition assessment. The system analyses pre-procedural CT scans to quantify Skeletal Muscle Index, Visceral Adipose Tissue, and Subcutaneous Adipose Tissue. The interface accepts DICOM files and patient data, generating comprehensive reports including segmented images and measurements. Results: System evaluation demonstrated an average analysis time of 21 seconds from upload to results display. User experience assessment with five clinicians showed unanimous positive feedback regarding acces- sibility and utility. Technical validation confirmed accurate tissue segmentation and quantification capabilities. Analysis of illustrative cases demonstrated significant discrepancies between BMI-based assessment and CT-derived body composition analysis, revealing conditions such as sarcopenic obesity and preserved muscle mass that would be missed by BMI evaluation alone. Conclusion: This technical solution provides an accessible, integrated approach to body composition assessment in TAVI patients. Building upon the validated AutoMATiCA software, the system successfully bridges the gap between complex analysis capabilities and clinical practicality through an intuitive user interface. This solution should enable more precise risk stratification and a more individualized approach to patients indicated for TAVI in the future.
Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units).
- Publication type
- Journal Article MeSH
- Review MeSH
Preterm prelabour rupture of membranes (PPROM) complicated by intra-amniotic inflammation (IAI) represents a substantial proportion of preterm birth cases. Currently, IAI is frequently defined as amniotic fluid IL-6 concentration above 2,600 pg/mL. However, the amniotic fluid IL-6 concentration was never correlated with the global response of other proinflammatory proteins to the ongoing IAI. In this cross-sectional study, protein quantification was performed using mass spectrometry (MS) analysis followed by target quantification of selected proinflammatory proteins. Levels of amniotic fluid proteins determined by MS were put into the correlation with IL-6 concentration determined by electrochemiluminescence immunoassay method (ECLIA). In total, 925 proteins were efficiently quantified and differential expression analysis revealed 378 proteins upregulated towards IL-6 concentration above 10,000 pg/mL. Four proteins (LCN2, MMP8, MPO, and S100A12) were selected to verify the achieved results and IL-6 concentration of 10,000 pg/mL was determined as the cut-off value for global IAI response.
- MeSH
- Biomarkers metabolism MeSH
- Chorioamnionitis * metabolism MeSH
- Adult MeSH
- Interleukin-6 metabolism MeSH
- Humans MeSH
- Amniotic Fluid * metabolism MeSH
- Fetal Membranes, Premature Rupture * metabolism pathology MeSH
- S100A12 Protein metabolism MeSH
- Cross-Sectional Studies MeSH
- Pregnancy MeSH
- Inflammation * metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
80letá pacientka s diabetem 2. typu byla pro neuspokojivou kompenzaci a symptomy hypoglykemie převedena z inzulínového režimu bazál-bolus s úspěchem na terapii IDegLira. Glykovaný hemoglobin se snížil ze 76 na 59 mmol/mol, příznaky hypoglykemie se neopakovaly, tělesná hmotnost se snížila z 88 na 82 kg. Celková pohoda a vitalita se zlepšily. Podmínkou úspěšné změny terapie byla kvantifikace postprandiální inzulínové sekrece (C-peptid nalačno 644,8 pmol/l, postprandiálně 1 782,2 pmol/l). Kazuistika dokládá pozitivní dopad změny terapie s využitím fixní kombinace dlouhodobě účinného inzulínového analoga degludek a liraglutidu (IDegLira) na kompenzaci diabetu, snížení rizika hypoglykemie a zlepšení životní pohody.
An 80-year-old female patient with type 2 diabetes was transferred, due to unsatisfactory diabetes control and hypoglycaemia symptoms, from basal-bolus insulin regimen to IDegLira therapy with success. Glycated haemoglobin was reduced from 76 to 59 mmol/mol, body weight was reduced from 88 to 82 kg, and hypoglycaemia symptoms did not recur. Overall well-being and vitality improved. The condition for a successful change in therapy was the quantification of postprandial insulin secretion (fasting C-peptide 644.8 pmol/l, postprandial 1,782.2 pmol/l). The case report proves the positive effect of therapy using a fixed combination of long-lasting insulin analogue degludec and liraglutide (IDegLira) on diabetes control, reducing the risk of hypoglycaemia and improvement of overall well-being.
